Protocol number 93-M-0170, NCT00001360 The Section on Functional Imaging Methods (SFIM) has advanced functional MRI (fMRI) methodology through development of processing and acquisition methods and research on the underlying mechanisms behind the fMRI signal. The ultimate goals are to grain a deeper understanding of healthy human brain and to apply fMRI clinically on an individual basis. Multi-echo fMRI to improve connectivity mapping This year's work on our novel and powerful method for separating noise from true fMRI signals (called ME-ICA) was directed towards applying it to better understand child development and principles of brain organization. We have two papers in the literature for this and have several more under review. In collaboration with Dr. Pine's group we delineated clear resting state network changes with development. Essentially, the methods reveal that children have many more independent networks than adults do. Simultaneous EEG and fMRI to detect ultra-slow brain changes. Following up on the above project, my post doc Jen Evans in collaboration with Silvina Horovitz (NINDS), acquired simultaneous EEG and multi-echo fMRI in conjunction with low frequency paradigms. EEG data gives us a direct neural measure of the low frequency task signal. We demonstrate that ME-ICA de-noised data better captures the neural components of the fMRI signal than conventional data. Contribution of non-conventional responses to wide-spread activations (7T study) Carried out by my staff scientist Javier Gonzalez-Castillo and post-bac IRTA Colin Hoy. This work constitutes an extension of our original observation of widespread BOLD activations to simple externally driven tasks. In our original study we showed how, when TSNR is sufficiently high and response models versatile enough, it is possible to detect BOLD signal changes correlated with task paradigm in the majority of the brain. In the present work, we show how these widespread activations are cognitive load dependent and are still present despite a significant increase (approximately six fold) in nominal spatial resolution. Spatial distribution of resting state connectivity stability (3T study) Carried out by my staff scientist Javier Gonzalez-Castillo, post-bac IRTA Colin Hoy and post-bac IRTA Laura Buchanan. The dynamic behavior of BOLD fMRI connectivity at short temporal scales (tens of seconds) is gaining attention and very little is known about the origin. In this project we acquired fMRI data continuously for 60 minutes as subjects rested in the scanner. We found that the most stable connections correspond primarily to inter-hemispheric connections between left/right homologous ROIs. The most variable connections correspond primarily to inter-hemispheric, across-network connections between non-homologous regions in occipital and frontal cortex. Whole brain connectivity dynamics and its relationship to on-going cognition (7T study) Carried out by my staff scientist Javier Gonzalez-Castillo, and post-bac Colin Hoy. As mentioned above, BOLD connectivity is quite volatile at short temporal scales. Given the complex nature of BOLD signals, such variability could be driven by a combination of neuronal and non-neuronal factors. The present study evaluates the potential relationship between BOLD connectivity dynamics at the scale of seconds to minutes with on-going cognition. We acquired functional data continuously for approximately 25 minutes as subjects engage and transition in four different cognitive states, namely rest, mathematical computation, a working memory task and a visual attention task. Our results show that it is possible to group together epochs corresponding to the same cognitive state based on whole-brain connectivity matrices computed with epochs ranging in duration from 3 m to 15 s with high levels of accuracy. Change in Hippocampal Myelination with Aerobic Exercise This project has been carried out by Adam Thomas, who has been recently granted his PhD from Oxford University. In collaboration with Dr. Heidi Johansen-Berg (also at Oxford) we have demonstrated volume growth in the anterior hippocampus after just six weeks of aerobic exercise. Previous rodent studies have shown the hippocampus to be a site of neurogenesis, which is facilitated by exercise. Using advanced statistical methods designed by Dr. Thomas Nichols at the University of Warwick, we were able to demonstrate that the change is dominated by myelination and not by grey matter or vasculature as other groups have predicted. This work has recently been submitted for peer review at a high impact journal. Cerebral blood volume and physical fitness This project has also been carried out by Adam Thomas as part of his thesis work. It has been previously demonstrated that physical fitness is associated with improved cognitive function, especially executive function and working memory. However remains unclear what the mechanism for this relationship may be. In this project, we used contrast agent injections in a large sample of health adults to quantify brain volume throughout the brain. We also measured physical fitness and working memory. We show that physical fitness is positively correlated with total cerebral brain volume, which in turn was positively correlated with physical fitness. Further analyses suggest that greater blood volume in the brain may be one mechanism by which greater fitness leads to improved cognitive function, perhaps by increased oxygen delivery. Hippocampal Morphometry and Depression In a collaborative project between Adam Thomas in my lab and the lab of Carlos Zarate, we have explored the detailed structure of the human hippocampus using high resolution 7 Tesla imaging. Previous studies have shown a tight link between hippocampal volume, neurogenesis, and depression symptoms. Using susceptibility-weighted scans that are sensitive to the myelinated pathway that parallels the dentate gyrus, a subfield of the hippocampus where neurogenesis occurs, we were able to reconstruct the complex curvature pattern of this structure and quantify its convolution using curvature metrics developed by Mark Jenkinson at Oxford University. We have shown that the degree of curvature shows a positive correlation with severity of depression. Functional laterality measured from Resting-state FMRI in human and monkey brain Carried out by my post doc Hang Joon Jo in collaboration with Dr. David Leopold and Dr. Alex Martin (both of NIMH). By resting-state FMRI analysis, we were able to extend the inter-hemispheric symmetry to the entire cerebrum. For this project, we developed novel methods for defining the anatomical and functional homologues between hemispheres. By those, we could study the laterality of RS-FMRI connectivity to identify functional laterality in human cortex, and also apply the methods and findings to individual subjects of non-human primates to provide more explicit interpretation for the cortical development and evolution in multiple species. For the monkey data, in the results, most cortical areas have the symmetric functional connections across two hemispheres, and this is highly relevant to the results of the same analysis in human brain. However, few areas in lateral frontal and parietal cortices showed different patterns in all subjects. We suggested that those regions might reflect the individual difference in functional lateralization.